Inhibition of enzymes by fatty acyl-CoA (palmityl, stearyl and oleoyl-CoA) has been demonstrated many times but because these compounds are good detergents (critical micelle concentration equals 3-4 micronM) the physiological significance of this inhibition with respect to lipid metabolism is still open to question. Very recently the principal investigator (Hsu & Powell, unpublished results) has prepared and characterized oleoyl-ethenoCoA, an oleoyl-CoA modified on the adenine moiety by an N1, N6-etheno bridge (Secrist, Barrio, Leonard & Weber. Biochem. 11 (1972) 3499), and shown that this analogue is also a good detergent (CMC equals 3.1 micronM. However the analogue is not as good an inhibitor of pig heart citrate synthase (50% inhibition at 40 micronM) as oleoyl-CoA (50% inhibition at 6 micronM) nor is it bound well as shown by equilibrium dialysis. Thus Hsu and Powell have shown that detergency alone does not cause the inhibition; a specific interaction with the adenine moiety is required. The principal investigator (G. L. Powell) proposes a collaboration with J. Jacobus to use magnetic resonance techniques to estimate the molecular motion of 16- and 5-doxylstearyl-CoA (Devaux, Bienvenue, Lanquin, Brisson, Vignais & Vignais, Biochem. 14 (1975) 1272) and of stearyl-CoA specifically deuterated on the acyl chain and of the H1 and H8 protons of the adenine moiety in association with micelles, biological membranes, and citrate synthase. This data should provide firm evidence for the binding of this compound to citrate synthase and provide a great deal of information about the binding and the inhibition of citrate synthase by fatty acyl-CoA. We propose extending this treatment to other enzymes involved in lipid metabolism. By establishing the existence of such binding sites and characterizing them we will establish a new mechanism for regulation of lipid metabolism which may have a significant impact on the treatment of heart disease, muscular dystrophy, and other less well characterized disorders of lipid metabolism.